Do We Truly Understand the Scope of GPLIs?

Abstract

Obesity and increasing diabetes mellitus are the bane of modern affluent society. An under-standing of the underlying pathophysiological constraints must be understood well any of us can embark upon treating patients of obesity or DM. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) were identified in crude form by indirect evidence between 1903 to 1930. The plasma half-life of the drugs prepared based on these findings was extremely short. Between 1995 to 2007 we refined their longer half-life formulations (Liraglutide) which facilitated their usage in the management of type 2 diabetes mellitus (T2DM) and obesity.¹ By 2015 (90hr) long half-life formulations (Dulaglutide, Semaglutide) became available which could be given on weekly basis.¹ By 2019 oral formulations had been given FDA approval for oral formulations (Semaglutide) revolutionizing the usage of the incretin based GLP1 Receptor Agonist. GLP-1 RAs have effects on multiple systems e.g. neuroprotective, anti-inflammatory, reductions in systemic inflammatory markers and effects on immune cell function, contribute to cardiovascular and metabolic benefits. Direct actions of gut include modulation of gut microbiome, preserving pancreatic beta-cell function and potentially promoting beta-cell regeneration¹.  GLP-1 RAs have revolutionized obesity management, demonstrated cardiovascular and renal protection, and have the promise to improve neurodegenerative disorders. Many unexplored applications of this group of medications show promise to further revolutionize prevention of cardiovascular events.^1-4